Transplantation. 2024 Mar 1;108(3):777-786 doi: 10.1097/TP.0000000000004841.
CET Conclusion
BACKGROUND:
Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD. METHODS:We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1. RESULTS:After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups. CONCLUSIONS:We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation. |
|||||||||||||||
Clin Infect Dis. 2024 Feb 17;78(2):312-323 doi: 10.1093/cid/ciad575.
CET Conclusion
BACKGROUND:
The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS:In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS:Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS:Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION:NCT02538172. |
|||||||||||||||
Lancet Respir Med. 2024 Jan;12(1):34-44 doi: 10.1016/S2213-2600(23)00293-X.
CET Conclusion
BACKGROUND:
Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. METHODS:ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (0·05-0·1 mg/kg before transplantation and 0·1-0·2 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27). FINDINGS:Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 55·2 years (SD 10·2), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 0·28 [95% CI 0·15-0·52], log-rank p<0·0001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 0·72 [95% CI 0·41-1·27], log-rank p=0·25). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 0·49 [95% CI 0·26-0·91], log-rank p=0·021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event. INTERPRETATION:Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation. FUNDING:Astellas, the ALF-agreement, Scandiatransplant Organization, and Heart Centre Research Committee, Rigshospitalet, Denmark. |
|||||||||||||||
Transplantation. 2024 Jan 1;108(1):261-275 doi: 10.1097/TP.0000000000004749.
CET Conclusion
BACKGROUND:
Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor. METHODS:This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease. RESULTS:There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m 2 , P = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P = 0.054). CONCLUSIONS:De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study. |
|||||||||||||||
Clin Transplant. 2023 Dec;37(12):e15139 doi: 10.1111/ctr.15139.
CET Conclusion
INTRODUCTION:
This study examines whether the use of inpatient Continuous Glucose Monitors provides improved glycemic control over finger-stick glucose monitoring post-transplant. METHODS:This is a single-site, prospective randomized controlled trial of 40 patients receiving conventional finger-stick glucose monitoring or continuous monitoring using the Medtronic Guardian Sensor 3 during the first 5 days post-transplant. Included patients were adult renal transplant recipients with a diagnosis of diabetes. Assessed endpoints included post-transplant daily median glucose level, hyperglycemic (≥180 mg/dL) and hypoglycemic (≤80 mg/dL) episodes, number of post-transplant bacterial infections and length of stay. RESULTS:Groups were well matched in demographic variables. Median daily glucose was significantly lower in the intervention group. There were also significantly less episodes of hyperglycemia on postoperative days 2, 3, 4, and 5. There were no differences in the incidences of hypoglycemia, postoperative bacterial infections, or length of stay. CONCLUSION:In this randomized study, the use of a continuous glucose monitor to guide post-transplant glucose management significantly lowered the incidence of hyperglycemic episodes and median glucose levels through the first 5 days post-transplant without increasing the number of hypoglycemic episodes. The use of these devices can be considered in the immediate post-renal transplant setting. |
|||||||||||||||
Transplant Rev (Orlando). 2023 Dec;37(4):100789 doi: 10.1016/j.trre.2023.100789.
CET Conclusion
BACKGROUND:
Renal transplant is the standard of care for patients with end-stage renal disease (ESRD). Robotic-assisted kidney transplant (RAKT) has emerged as a safe minimally invasive approach with a lower complication rate than open kidney transplant (OKT). Concerns regarding ischemia times and graft function are still a matter of debate. METHODS:Following PRISMA guidelines and PROSPERO registration CRD42023413774, a systematic review was performed in March 2023 on RAKT compared to OKT. Primary outcomes of interest were surgical times, ischemia times, blood loss, complication rates, and graft function. Data were analyzed using R version 4.2.2. RESULTS:A total of nine studies comparing living donor RAKT to living donor OKT were included, totaling 1477 patients, out of which 508 underwent RAKT and 969 OKT. RAKT cases were highly selected as depicted in the manuscript. Cumulative analysis showed significantly longer total ischemic time (MD = 16.51; 95% CI = [9.86-23.16]) and rewarming ischemia time (MD = 11.24; 95% CI = [-0.46-22.01]) in RAKT group. No differences were found in total procedure time and time to complete anastomoses. Blood loss and transfusion rate were lower in RAKT group (MD = -53.68; 95% CI = [-89.78; -17.58]) and (RR = 0.29; 95% CI = [0.14; 0.57]), respectively. The meta-analysis revealed a lower rate of surgical site infection (SSI) (RR = 0.31; 95% CI = [0.19-0.52]) and symptomatic lymphocele (RR = 0.16; 95% CI = [0.06-0.43]) in RAKT. No difference in ileus rate was found. Pain scores were significantly lower in the RAKT group (MD = -1.14; 95% CI = [-1.59 - -0.69]; p ≤0.01). No difference in length of stay and hospital readmission were evidenced. Delayed graft function (DGF) and acute rejection rates were not different between interventions groups (RR =1.23; 95% CI = [0.40-3.74]) and (RR =0.96; 95% CI = [0.55-1.70]), respectively. No difference between groups in early graft outcomes are evident. CONCLUSIONS:Our analysis suggests that RAKT is a minimally invasive, safe, and feasible procedure. It is associated with a lower complication rate and similar intraoperative, perioperative, and postoperative outcomes. Further quality studies are needed to confirm these findings. |
|||||||||||||||
Transplantation. 2023 Dec 1;107(12):2568-2574 doi: 10.1097/TP.0000000000004712.
CET Conclusion
BACKGROUND:
Urine CXCL10 is a biomarker for renal allograft inflammation induced by rejection, urinary tract infection, or BK polyomavirus (BKPyV) replication. This study aimed to compare urine CXCL10 levels in different stages of BKPyV reactivation and to investigate urine CXCL10 as a biomarker for BKPyV replication. METHODS:We included 763 urine samples (235 patients) from an interventional, randomized trial obtained in the context of regular screening for urine CXCL10 levels. All urine samples had a complete urine sediment analysis, no rejection episode noted within 30 d before urine collection, and a urine decoy cell analysis was conducted within ±3 d. RESULTS:Urine CXCL10 levels were 2.31 ng/mmol in samples without BKPyV viruria, slightly rose to 4.35 ng/mmol with BKPyV viruria, and then markedly increased to 16.42 ng/mmol when decoy cells were detectable, but still in the absence of BKPyV DNAemia ( P < 0.001). The highest urine CXCL10 values were observed in samples with BKPyV DNAemia (median 42.59 ng/mmol). The area under the curve of urine CXCL10 levels to detect ≥3 decoy cells was 0.816. At a CXCL10 cutoff of 3 ng/mmol, the negative predictive value was 97%. The area under the curve of urine CXCL10 levels to detect BKPyV DNAemia was 0.882, with a negative predictive value of 99% at a CXCL10 cutoff of 3 ng/mmol. CONCLUSIONS:Urine CXCL10 levels are already significantly elevated in BKPyV viruria (especially with decoy cell shedding) and further increase with BKPyV DNAemia. Low urine CXCL10 values can rule out the presence of ≥3 decoy cells and BKPyV DNAemia with high certainty. |
|||||||||||||||
BMC Res Notes. 2023 Oct 26;16(1):295 doi: 10.1186/s13104-023-06568-9.
CET Conclusion
INTRODUCTION:
Simultaneous pancreas kidney (SPK) transplantation is an invaluable procedure to enhance the quality of life of insulin-dependent patients with advanced renal disease. The creation of vascular anastomoses of the donor's pancreas vessels to the recipient's, is of utmost importance to predict the graft outcome and surgical complications. In the study we introduce a novel technique for arterial reconstruction during SPK transplantation. METHODS:Conventionally, during the SPK transplantation, a so-called Y-graft is anastomosed between donor's superior mesenteric and splenic artery to the recipient's right iliac artery. In the study we adopted a new technique by preparing an extra extension using the donor's carotid artery, to be anastomosed to the Y-graft and the iliac artery. In this non-blinded randomized clinical trial we compared the surgical complications and early outcomes between the 2 groups of patients with the traditional and new arterial reconstruction techniques during 3 months after transplantation. RESULTS:Thirty adult patients were included in the study. The incidence of pancreatitis, vascular thrombosis and surgical site infection was lower in the new Y-graft and extension technique, which was not statistically significant. However, the calculated Cohen's d index showed the medium effect of new Y-graft and extension technique on complication after SPK transplantations. CONCLUSION:The post-operative complications tend to be lower in the novel arterial reconstruction technique, however a study on a larger patient group is encouraged to confirm our primary results. TRIAL REGISTRATION:The study was registered at the Iranian Registry of Clinical Trials on 12/05/2022; IRCT 20210625051701N2; ( http://www.irct.ir/ ). |
|||||||||||||||
Exp Clin Transplant. 2023 Oct;21(10):814-819 doi: 10.6002/ect.2023.0071.
CET Conclusion
OBJECTIVES:
Nephropathy due to BK virus infection is a major cause of graft dysfunction and loss. No specific treatment has been developed for the BK virus. Here, we compared the combination of intravenous immunoglobulin and leflunomide versus intravenous immunoglobulin to treat BK virus nephropathy after renal transplant. MATERIALS AND METHODS:This study was a randomized controlled clinical trial. Sixteen kidney transplant patients with BK virus infection were randomly divided into 2 groups; 1 group received intravenous immunoglobulin, and another group received leflunomide and intravenous immunoglobulin. P < .05 was considered statistically significant. RESULTS:Results of a polymerase chain reaction test for BK virus after 2 months of treatment were negative in 3 patients in the intravenous immunoglobulin group and in 7 patients in the intravenous immunoglobulin + leflunomide group. The amount of BK virus decreased significantly in each group, and a significant difference was observed between the 2 groups after 3 months (P = .014). The average level of creatinine in the intravenous immunoglobulin group at 1, 2, and 3 months after treatment was 1.7 ± 0.23, 1.8 ± 0.5, and 1.5 ± 0.3, respectively, and in the intravenous immunoglobulin + leflunomide group was 2.1 ± 0.75, 1.76 ± 0.37, and 1.4 ± 0.18, respectively (P > .05). CONCLUSIONS:Although BK viral load decreased significantly in both groups, there was a significant difference between patients who received intravenous immunoglobulin versus those who received the combination of intravenous immunoglobulin + leflunomide after 3 months. The addition of leflunomide to the intravenous immunoglobulin treatment seems to have a better effect in reducing BK viral load. However, further studies with a larger sample and longer duration are needed. |
|||||||||||||||
BMC Nephrol. 2023 Sep 27;24(1):284 doi: 10.1186/s12882-023-03338-4.
CET Conclusion
BACKGROUND:
A kidney recipient's urinary tract infection (UTI) can result in infectious problems and be a risk factor for less successful transplant outcomes. UTI risk factors are still controversial. The present study aimed to investigate the prevalence of UTI and its association with risk factors in kidney recipients. METHOD:Twenty-six papers published between 2005 and 2022 were retrieved using keywords and searching Medlib, ScienceDirect, PubMed, and other databases. If possible, the pooled prevalence of UTI in kidney recipients and odds ratio (OR) with a 95% confidence interval for each risk factor were calculated. The data were analyzed using the random effects model in R and Stata 14. RESULTS:The total sample size was 72,600, with an average age of 48.7 years. The pooled prevalence of UTI was 35% (95% CI, 30-40%). The estimated risk factors for UTI were female (OR = 3.13; 95%CI: 2.35-4.17), older age (OR = 1.03; 95%CI: 1-1.05), history of UTI (OR = 1.31; 95%CI) CI: 1.05-1.63), receiving a kidney from a deceased donor (OR = 1.59; 95%CI: 1.23-2.35), long-term use of an indwelling catheter (OR = 3.03; 95%CI: 1.59-6.59), a ureteral stent (OR = 1.54; 95%CI: 1.16-2.06), diabetes (OR = 1.17; 95%CI: 0.97-1.41), hypertension (OR = 1.6; 95%CI: 1.26-2.28), acute rejection process (OR = 2.22; 95%CI: 1.45-3.4), and abnormal urinary tract anatomy (OR = 2.87; 95%CI 1.44-5.74). CONCLUSION:This meta-analysis revealed that UTIs are a significant problem in kidney recipients. Factors such as female sex, old age, history of UTIs, deceased donor, long-term use of an indwelling catheter, diabetes, acute rejection process, use of ureteral stent, abnormal urinary tract anatomy, and hypertension were related to an increased risk of UTIs in kidney recipients. |